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A ribozyme ligase that requires a 3′ terminal phosphate on its RNA substrate
Abstract Ribozymes likely played essential roles in catalyzing metabolic processes and facilitating genome replication in primordial RNA-based life. In vitro evolution has allowed us to expand the biochemical capabilities of RNA, especially new ribozyme chemistries. Here, we report the serendipitous discovery of ribozyme ligases that catalyze the attack of the 2′-hydroxyl group of an RNA substrate on its own 5′-triphosphate group, but only when the substrate possesses a 3′-phosphate vicinal to its nucleophilic 2′-hydroxyl group. The ligases′ requirement for a 3′-phosphate group on its substrate resembles enzymatic mechanisms found in protein-based RNA repair pathways. We propose that ribozyme-catalyzed ligation of 3′-phosphorylated RNA could have provided pathways for RNA repair in primordial cells. We demonstrate that these ribozymes ligate specifically to 3′-phosphorylated RNA present in a heterogeneous mixture of cellular RNAs. We further show that these ribozymes can capture cleaved RNAs with 3′-phosphate and 2′−3′-cyclic phosphate termini, enabling us to selectively amplify the captured RNAs. These results demonstrate their potential utility as enrichment reagents for profiling RNA cleavage products in transcriptomics studies. Our findings not only report a new catalytic reactivity in RNA but also provide insights into ribozyme evolution, primordial RNA repair, and potential applications in RNA sequencing.
Effects of an 18-week postpartum rehabilitation and physical development intervention on occupational physical performance in UK servicewomen
Abstract Physiological and psychological changes following childbirth can increase injury risk, and reduce physical performance in servicewomen, yet evidence to inform guidelines for preparing postpartum servicewomen to return to military service is limited. This study examined the efficacy of a rehabilitation and physical development intervention for returning servicewomen to occupational fitness postpartum. UK-based servicewomen were assigned to a training (INT; N = 17) or control (CON; N = 14) group 6-weeks postpartum in a non-randomised controlled trial. CON received standard postpartum care, whilst INT received standard care plus an 18-week rehabilitation (core and pelvic floor exercises) and supervised physical development (resistance training and HIIT) programme. Participants were assessed between 6 and 24 weeks postpartum for occupational performance (primary outcome) and pelvic health, psychological well-being, and musculoskeletal health (secondary outcomes). 11 INT and 9 CON participants completed all visits. INT participants demonstrated high adherence to core reconnection and physical development training (96%) and reported no adverse events. Significant group x time interactions favouring INT were shown for occupational performance outcomes, including mid-thigh pull, vertical jump, and 2 km run time-trial (all p ≤ 0.05, 12.7–14.5% improvements), but not for medicine ball throw ( p = 0.643). INT had superior improvements over CON in body composition, pelvic health, and psychological well-being (all p < 0. 05). A combined rehabilitation and physical development programme was well-adhered to, did not result in any adverse events, and was more effective than standard postpartum care in improving occupational performance, pelvic health, body composition, and psychological well-being amongst servicewomen. These findings help inform best-practice guidelines for returning postpartum servicewomen to occupational fitness. Trial registration: ClinicalTrials.gov NCT04332757, Date 05/2021.
Southern Ocean regime shift: divergent trends in surface phytoplankton community composition using a diagnostic pigment framework
Chemotherapy was not independently associated with cancer-specific death in non-metastatic right-sided colon neuroendocrine carcinoma from SEER
Nrf2-mediated metabolic reprogramming drives regulatory T cell accumulation in hepatocellular carcinoma
Abstract Excessive recruitment and/or activation of regulatory T cells (Treg) into the tumour microenvironment (TME) hamper anti-cancer immunity. Targeting Tregs is therefore a promising strategy to reverse the immunosuppressive features of the TME. Here, we investigate how the development of hepatocellular carcinoma (HCC) impacts the molecular programmes of tissue-resident Tregs. Tregs residing in non-tumoral liver are metabolically inert and prone to apoptosis. Conversely, HCC-infiltrating Tregs activate the nuclear factor erythroid 2-related factor-2 (Nrf2) pathway in response to the lactate-rich TME, which couples redox homeostasis with mitochondrial function and promotes Treg metabolic activity, survival, and suppressive function. Nrf2 loss of function, through either Treg-specific Nfe2l2 ablation or systemic pharmacological inhibition, prevents intra-tumoral Treg accumulation and suppresses cancer growth. Furthermore, patients with advanced HCCs enriched in Tregs with high Nrf2 activation exhibit shorter progression-free survival following atezolizumab/bevacizumab treatment. We propose Nrf2 as a target to disrupt Treg metabolic adaptation within the TME, tipping the balance between effector and regulatory immune cells and reducing cancer progression.
The association between gestational vitamin D levels and offspring vitamin D receptor polymorphisms in autism-associated traits
Divergent mechanisms of active antibiotic resistance gene enrichment in soil driven by pesticide diversity
Industrial jarosite as a functional pigment in epoxy and alkyd anticorrosive coatings
CaO-loaded cellulose acetate electrospun composite fibers: morphological, structural, and functional evaluation for biomedical applications
Abstract This study presents a novel and sustainable approach for the fabrication of electrospun cellulose acetate (CA)/calcium oxide (CaO) composite fibers by utilizing bioactive CaO nanoparticles derived from calcined waste eggshells as an eco-friendly inorganic filler for advanced biomedical applications. CA/CaO composite solutions were prepared by mixing CaO powder of various proportions into a 10% CA solution and processed via electrospinning to produce composite fibers. The findings confirm the successful transformation of calcium carbonate (CaCO₃) into CaO through thermal calcination process. CaO particles were successfully incorporated into the fibers, with the median fiber diameter decreasing after CaO incorporation. Among the investigated samples, the CA/CaO composite fibers containing 2–6 wt% CaO showed the most favorable properties, providing a balance between fiber diameter, morphology, controlled and gradual calcium release in prepared phosphate-buffered saline (PBS), and chemical stability in prepared simulated body fluid solution (SPF).The hydrophilicity and water spreading behavior were improved by the incorporation of CaO particles, as evidenced by the reduction in the contact angle to 60° compared with 81° for pure CA fibers. These results highlight an emerging method for producing novel biodegradable CA/CaO polymer composites with adjustable properties and enhanced hydrophilicity, providing a basis for future investigations of their suitability for biomedical applications.
Enhanced variants of the Musk Ox Optimizer for global optimization problems
Structural predictability differences in long-term regional crop yield modeling with climate and area signals
Abstract Climate-driven crop yield modeling has been widely studied; however, the marginal predictive value of climate signals relative to temporal persistence remains insufficiently examined at the annual regional scale. This study investigates structural differences in long-term yield predictability using anonymized multi-region panel data spanning 2000–2023. A pooled one-step-ahead machine learning forecasting framework was constructed and evaluated against a naïve persistence baseline to assess the additional contribution of climate and area signals. Results reveal clear crop-specific heterogeneity. For cotton, climate-only models provide limited predictive skill, whereas incorporating planting area substantially improves performance, achieving a test R 2 of approximately 0.72, comparable to the persistence baseline (R 2 = 0.71). In contrast, wheat exhibits persistence-dominated predictability in the pooled dataset, with the persistence model achieving a test R 2 of 0.99. Additional analyses revealed that this high predictive performance is primarily associated with stable between-region differences rather than exceptionally strong within-region temporal persistence. These findings suggest that annual regional yield predictability is strongly crop-dependent and may be constrained by the temporal stability of the production system. Climate signals alone were insufficient to outperform persistence under the annual aggregation setting used in this study. Persistence may account for a large proportion of predictable variation in highly stable crop systems. However, these results should be interpreted as scale- and data-specific evidence rather than as a definitive assessment of climate-driven yield predictability. The findings highlight the importance of persistence-aware evaluation and careful benchmark design in agricultural forecasting research.